| Autor: |
Schwartz, Mathias, Ibadioune, Sabrina, Chansavang, Albain, Vacher, Sophie, Caputo, Sandrine M, Delhomelle, Hélène, Wong, Jennifer, Abidallah, Khadija, Moncoutier, Virginie, Becette, Véronique, Popova, Tatiana, Suybeng, Voreak, De Pauw, Antoine, Stern, Marc-Henri, Colas, Chrystelle, Mouret-Fourme, Emmanuelle, Stoppa-Lyonnet, Dominique, Golmard, Lisa, Bieche, Ivan, Masliah-Planchon, Julien |
| Zdroj: |
Journal of Medical Genetics (JMG); 2024, Vol. 61 Issue: 3 p284-288, 5p |
| Abstrakt: |
PurposeMosaic BRCA1promoter methylation (BRCA1meth) increases the risk of early-onset breast cancer, triple-negative breast cancer and ovarian cancer. As mosaic BRCA1meth are believed to occur de novo, their role in family breast/ovarian cancer has not been assessed.PatientsBlood-derived DNA from 20 unrelated affected cases from families with aggregation of breast/ovarian cancer, but with no germline pathogenic variants in BRCA1/2, PALB2or RAD51C/D, were screened by methylation-sensitive high-resolution melting. CpG analysis was performed by pyrosequencing on blood and buccal swab. Two probands carried a pathogenic variant in a moderate-penetrance gene (ATMand BARD1), and 8 of 18 others (44%) carried BRCA1meth (vs none of the 20 age-matched controls). Involvement of BRCA1in tumourigenesis in methylated probands was demonstrated in most tested cases by detection of a loss of heterozygosity and a homologous recombination deficiency signature. Among the eight methylated probands, two had relatives with breast cancer with detectable BRCA1meth in blood, including one with high methylation levels in two non-tumour tissues.ConclusionsThe high prevalence of mosaic BRCA1meth in patients with breast/ovarian cancer with affected relatives, as well as this first description of a family aggregation of mosaic BRCA1meth, shows how this de novo event can contribute to hereditary breast/ovarian cancer pedigrees. |
| Databáze: |
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